Tumorigenic activity of fluoranthene, 2-methylfluoranthene and 3-methylfluoranthene in newborn CD-1 mice. 1994

E J LaVoie, and Z W Cai, and C L Meschter, and E H Weyand
Department of Pharmaceutical Chemistry, Rutgers, State University of New Jersey, College of Pharmacy, Piscataway 08855.

Fluoranthene (FA) is frequently among the more abundant components detected in environmental mixtures of polycyclic aromatic hydrocarbons. Several methylated fluoranthenes, although less prevalent than FA, have also been detected as environmental pollutants. While FA is inactive as a tumorigenic agent on mouse skin, it does induce lung and liver tumors in newborn mice. Among the five isomers of methylfluoranthene, only 2-methylfluoranthene (2-MeFA) and 3-methylfluoranthene (3-MeFA) are active as tumor initiators on mouse skin. A comparative bioassay was performed to determine the relative tumorigenic activity of FA, 2-MeFA and 3-MeFA in newborn CD-1 mice. All three compounds were assayed at doses of 3.46 and 17.3 mumol. The bioassay was terminated when mice were 1 year old. At a dose of 17.3 mumol, FA and 2-MeFA induced a similar incidence of lung tumors (65-96%) in both male and female mice. However, tumor multiplicity in the lung was different between FA and 2-MeFA. At a dose of 17.3 mumol, the multiplicity of lung tumors observed for mice administered 2-MeFA ranged from 3.04 to 3.94 tumors per mouse. In contrast, animals treated with FA developed only an average of 1.12-2.45 tumors per mouse. 3-MeFA did not induce a statistically significant incidence of lung tumors in either male or female mice. All three compounds when administered to newborn mice did induce a significant incidence of liver tumors among male mice. The relative tumorigenic potency observed was FA > or = 2-MeFa >> 3-MeFA. Only 2-MeFA at a dose of 17.3 mumol was tumorigenic in the liver of female mice. These bioassay results are contrasted with prior studies on the in vitro genotoxic activity and metabolic activation pathways of FA, 2-MeFA and 3-MeFA.

UI MeSH Term Description Entries
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002282 Adenocarcinoma, Bronchiolo-Alveolar A carcinoma derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed) Carcinoma, Alveolar,Carcinoma, Bronchiolar,Carcinoma, Bronchiolo-Alveolar,Adenocarcinoma, Alveolar,Alveolar Cell Carcinoma,Carcinoma, Bronchioloalveolar,Adenocarcinoma, Bronchiolo Alveolar,Adenocarcinomas, Alveolar,Adenocarcinomas, Bronchiolo-Alveolar,Alveolar Adenocarcinoma,Alveolar Adenocarcinomas,Alveolar Carcinoma,Alveolar Carcinomas,Alveolar Cell Carcinomas,Bronchiolar Carcinoma,Bronchiolar Carcinomas,Bronchiolo-Alveolar Adenocarcinoma,Bronchiolo-Alveolar Adenocarcinomas,Bronchiolo-Alveolar Carcinoma,Bronchiolo-Alveolar Carcinomas,Bronchioloalveolar Carcinoma,Bronchioloalveolar Carcinomas,Carcinoma, Alveolar Cell,Carcinoma, Bronchiolo Alveolar,Carcinomas, Alveolar,Carcinomas, Alveolar Cell,Carcinomas, Bronchiolar,Carcinomas, Bronchiolo-Alveolar,Carcinomas, Bronchioloalveolar
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005449 Fluorenes A family of diphenylenemethane derivatives.

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